DNA chips have attracted attention as a tool, for example, for simultaneous genetic diagnosis for many items, simultaneous examination of many types of mRNAs for expression level, and simultaneous examination for many single nucleotide polymorphisms (SNPs). DNA chips, also called DNA microarrays, are probe arrays using known DNAs that hybridize with target DNA molecules or RNA molecules as probes, having a plurality of types of probes held on a plurality of periodically arranged probe-holding portions.
In addition, antigen chips and antibody chips have attracted attention as a tool used for simultaneous examination for the presence or absence of many types of antigens or antibodies. Antigen chips are probe arrays using known antigens that bind to target antibody molecules as probes, having a plurality of types of probes held on a plurality of periodically arranged probe-holding portions. Antibody chips are probe arrays using known antibody molecules that bind to target antigens as probes, having a plurality of types of probes held on a plurality of periodically arranged probe-holding portions.
As a common method for producing a probe array, a method is known in which probe solutions (solutions containing probe molecules) are deposited in a dot pattern on a substrate such as a glass slide (hereinafter referred to as “spotting”) so that the probe molecules chemically bond to the surface of the substrate, thereby arranging probe spots on the surface of the substrate. Specifically, known spotting methods include a method in which a probe solution is ejected onto a substrate using an injection needle or a micropipette or by inkjet ejection and a method in which a probe solution placed at a needle tip is brought into contact with a substrate.
For the method using spotting, for example, Japanese Unexamined Patent Application Publication No. 2004-45055 (Patent Document 1) discloses a micropipette used for densely arranging droplets of extremely small volume. In addition, for example, Japanese Unexamined Patent Application Publication No. 2004-4076 (Patent Document 2) discloses a method for producing an array substrate configured to allow droplets supplied from a micropipette to be efficiently arranged thereon and to prevent the droplets from being mixed.
A probe array is preferably capable of having as many types of probes (probes holding different types of probe molecules or probes themselves) as possible arranged within a specific area. That is, a probe array having a higher packing density (number of spots arranged per unit area) is preferred. There is a problem, however, in that a probe array having a sufficiently high packing density cannot be produced because the spot area increases as the spotted probe solutions spread over the substrate.
In addition, the probe spots on the probe array need to hold sufficient amounts of probe molecules. If the probes hold insufficient amounts of probe molecules, it is difficult to detect target molecules because insufficient amounts of target molecules are bound to or hybridized with the probes. However, if the packing density of the probe array is increased, the spot area is decreased, and consequently the probe spots tend to contain insufficient amounts of probe molecules, often leading to the problem of insufficient detection sensitivity for target molecules.
In addition, the amounts of probe molecules held in the probes on the probe array are preferably constant and vary little. If the amounts of probe molecules held in the probes vary, the amounts of target molecules bound to or hybridized with the probes vary even through the concentrations of the target molecules in the solution under examination remain the same, thus leading to the problem that the concentrations of the target molecules in the solution under examination cannot be accurately determined because of varying signal strengths. The method using spotting, however, has a problem in that the amounts of probe molecules held at the probe spots tend to vary because the amounts of probe solutions spotted on the substrate tend to vary.
The above problems are particularly serious in the production of a probe array having high packing density. This is because extremely small amounts of probe solutions are spotted in the production of a probe array having high packing density and therefore slight variations in the amounts of probe solutions are more influential.    [Patent Document 1] Japanese Unexamined Patent Application Publication No. 2004-45055    [Patent Document 2] Japanese Unexamined Patent Application Publication No. 2004-4076